Light Delivery Research Articles

A Series of Personalized Virtual Light Therapy Interventions for Fatigue: Feasibility Randomized Crossover Trial for N-of-1 Treatment.

Fatigue is one of the most common symptoms treated in primary care and can lead to deficits in mental health and functioning. Light therapy can be an effective treatment for symptoms of fatigue; however, the feasibility, scalability, and individual-level heterogeneity of light therapy for fatigue are unknown. This study aimed to evaluate the feasibility, acceptability, and effectiveness of a series of personalized (N-of-1) interventions for the virtual delivery of bright light (BL) therapy and dim light (DL) therapy versus usual care (UC) treatment for fatigue in 60 participants. Participants completed satisfaction surveys comprising the System Usability Scale (SUS) and items assessing satisfaction with the components of the personalized trial. Symptoms of fatigue were measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) daily, PROMIS weekly, and ecological momentary assessment (EMA) questionnaires delivered 3 times daily. Comparisons of fatigue between the BL, DL, and UC treatment periods were conducted using generalized linear mixed model analyses between participants and generalized least squares analyses within individual participants. Participants rated the usability of the personalized trial as acceptable (average SUS score=78.9, SD 15.6), and 92% (49/53) of those who completed satisfaction surveys stated that they would recommend the trial to others. The levels of fatigue symptoms measured using the PROMIS daily fatigue measure were lower or improved in the BL (B=-1.63, 95% CI -2.63 to -0.63) and DL (B=-1.44, 95% CI -2.50 to -0.38) periods relative to UC. The treatment effects of BL and DL on the PROMIS daily measure varied among participants. Similar findings were demonstrated for the PROMIS weekly and EMA measures of fatigue symptoms. The participant scores on the SUS and satisfaction surveys suggest that personalized N-of-1 trials of light therapy for fatigue symptoms are both feasible and acceptable. Both interventions produced significant (P<.05) reductions in participant-reported PROMIS and EMA fatigue symptoms relative to UC. However, the heterogeneity of these treatment effects across participants indicated that the effect of light therapy was not uniform. This heterogeneity along with high ratings of usability and satisfaction support the use of personalized N-of-1 research designs in evaluating the effect of light therapy on fatigue for each patient. Furthermore, the results of this trial provide additional support for the use of a series of personalized N-of-1 research trials. ClinicalTrials.gov NCT04707846; https://clinicaltrials.gov/ct2/show/NCT04707846.

Application of Photodynamic Therapy in Pediatric Dentistry: Literature Review.

Microbiological control of dental pathologies presents a significant clinical challenge for dental surgeons, particularly considering drug-resistant microorganisms. To address this issue, Antimicrobial Photodynamic Therapy (PDT) has emerged as an effective and complementary technique for microbial reduction. This therapy involves the application of a photosensitizer dye (PS) either topically or systemically, followed by exposure to low-power lasers with appropriate visible light wavelengths. PDT has found a valuable place in dentistry across various specialties, including surgery, periodontics, endodontics, dentistry, implantology, orthodontics, and pediatrics. In the realm of pediatric dentistry, managing microorganisms during dental treatments has become a major challenge. Considering its promising results and ease of application, Photodynamic Therapy presents an interesting alternative for clinical practice. However, it is important to note that specific protocols must be followed for each application, encompassing the type of photosensitizer, concentration, pre-irradiation time, light type, wavelength, energy, power, and mode of light delivery. Researchers have been steadily refining these protocols to facilitate PDT's integration into clinical practice. The objective of this review is to describe in which procedures and oral health problems in children PDT can be applied. In this sense, we list what the literature brings about the possibilities of applying PDT in a pediatric dentistry clinic.

A floatable hydrogel-based photocatalytic system for large-scale solar hydrogen production

The effectiveness of scaling up photocatalysis is constrained by the agglomeration of photocatalysts. A floatable hydrogel-based photocatalytic system at the air-water interface reported by Hyeon et al. in the current issue of Nature Nanotechnology offers benefits for scaling up solar H2 production with effective light delivery and fast gas separation.

Near-Infrared Light-Controlled MicroRNA-21-Loaded Upconversion Nanoparticles to Promote Bone Formation in the Midpalatal Suture.

Rapid maxillary expansion (RME) is a common therapy for maxillary transverse deficiency. However, relapses after RME usually occur because of insufficient bone formation. MicroRNA-21 (miR-21) was reported as an important post-transcriptional modulator for osteogenesis. Herein, a photocontrolled miR-21 (PC-miR-21)-loaded nanosystem using upconversion nanoparticles (UCNPs) modified with poly(ether imide) (PEI), i.e., UCNPs@PEI@PC-miR-21, was constructed to promote bone formation in the midpalatal suture. UCNPs@PEI was constructed as the light transducer and delivery carrier. The UCNPs@PEI@PC-miR-21 nanocomplexes have good aqueous dispersibility and biocompatibility. The in vitro cell experiment suggested that UCNPs@PEI could protect PC-miR-21 from biodegradation and release PC-miR-21 into the cytoplasm under near-infrared light (NIR) irradiation. Furthermore, UCNPs@PEI@PC-miR-21 upregulated the expression of the osteogenic key markers, ALP, RUNX2, and COL1A1, at the levels of both genes and proteins. Besides, the results of the in vivo RME mice models further corroborated that photocontrollable UCNPs@PEI@PC-miR-21 accelerated bone formation with upregulating osteogenic markers of ALP, RUNX2, and osteoprotegerin and inducing fewer osteoclasts formation. In conclusion, UCNPs@PEI@PC-miR-21 nanoparticles with a NIR light could facilitate the remote and precise delivery of exogenous miR-21 to the midpalatal suture to promote bone formation during RME. This work represents a cutting-edge approach of gene therapy to promote osteogenesis in the midpalatal suture during RME and provides a frontier scientific basis for later clinical treatment.

Diya – A universal light illumination platform for multiwell plate cultures

Recent progress in protein engineering has established optogenetics as one of the leading external non-invasive stimulation strategies, with many optogenetic tools being designed for invivo operation. Characterization and optimization of these tools require a high-throughput and versatile light delivery system targeting micro-titer culture volumes. Here, we present a universal light illumination platform- Diya, compatible with a wide range of cell culture plates and dishes. Diya hosts specially designed features ensuring active thermal management, homogeneous illumination, and minimal light bleedthrough. It offers light induction programming via a user-friendly custom-designed GUI. Through extensive characterization experiments with multiple optogenetic tools in diverse model organisms (bacteria, yeast, and human cell lines), we show that Diya maintains viable conditions for cell cultures undergoing light induction. Finally, we demonstrate an optogenetic strategy for invivo biomolecular controller operation. With a custom-designed antithetic integral feedback circuit, we exhibit robust perfect adaptation and light-controlled set-point variation using Diya.

High-Density Integration of Ultrabright OLEDs on a Miniaturized Needle-Shaped CMOS Backplane.

Direct deposition of organic light-emitting diodes (OLEDs) on silicon-based complementary metal-oxide-semiconductor (CMOS) chips has enabled self-emissive microdisplays with high resolution and fill-factor. Emerging applications of OLEDs in augmented and virtual reality (AR/VR) displays and in biomedical applications, e.g., as brain implants for cell-specific light delivery in optogenetics, require light intensities orders of magnitude above those found in traditional displays. Further requirements often include a microscopic device footprint, a specific shape and ultrastable passivation, e.g., to ensure biocompatibility and minimal invasiveness of OLED-based implants. In this work, up to 1024 ultrabright, microscopic OLEDs are deposited directly on needle-shaped CMOS chips. Transmission electron microscopy and energy-dispersive X-ray spectroscopy are performed on the foundry-provided aluminum contact pads of the CMOS chips to guide a systematic optimization of the contacts. Plasma treatment and implementation of silver interlayers lead to ohmic contact conditions and thus facilitate direct vacuum deposition of orange- and blue-emitting OLED stacks leading to micrometer-sized pixels on the chips. The electronics in each needle allow each pixel to switch individually. The OLED pixels generate a mean optical power density of 0.25mWmm-2, corresponding to >40000cdm-2, well above the requirement for daylight AR applications and optogenetic single-unit activation in the brain.

Novel nanomaterials as photo‐activated cancer diagnostics and therapy

AbstractThe word “theranostics” describes an emerging trend in medicine in which the distinction between diagnosis and therapy blurs. Light or photo is used in theranostics to obtain high precision and personalised treatment. As only malignant tissues need to be spared, photo‐triggered theranostics provide highly selective targeting using real‐time imaging. Using nanotechnology to organise a dual‐modality approach is an efficient way to circumvent pharmacokinetic limitations. Photodynamic therapy has been used successfully in the clinic for a while now, and this has paved the path for photo‐triggered theranostics to be developed. The use of light‐activated theranostic nanoforms has progressed from preclinical studies in animals and labs to clinical trials in humans. As both nanomaterials and their methods of manufacture advance, the theranostic approach becomes more nuanced and may be used in a wider range of real‐time imaging and therapy modalities. The depth of anatomical access is also expanding because of developments in light delivery technologies. Combined, these innovations will hasten early cancer diagnosis and make tailored treatment more feasible. A non‐invasive assessment approach also increases patient compliance and reduces risk. Researchers constantly make strides in their effort to create more versatile photo‐sensitive nanoparticles. With any luck, photo‐triggered theranostics may significantly reduce toxicity. In order to provide a better and safer clinical outcome in cancer therapy, this review aims to highlight the latest and greatest innovation research in the domain of nanotheranostics and its photo‐triggering, and to sketch the possibilities for further progression and integration of nanoconstructs and photo‐delivery, and trying to target approach in photo‐triggered theranostics.

Advanced manufacturing of microscale light-emitting diodes and their use in displays and biomedicine

Thin-film, microscale light-emitting diodes (micro-LEDs)-based III–V compound semiconductors are emerging as a promising technology for next-generation light sources with various applications including lighting, display and biomedicine. With this perspective, we provide an overview and highlight our own progress on the recent developments in advanced manufacturing techniques and potential applications of micro-LEDs. The combination of epitaxial lift-off and transfer printing techniques have produced ultraminiaturized, highly luminous, and energy-efficient thin-film micro-LEDs, with a wide range of applications. To achieve full-color displays, several approaches have been developed, including horizontally and vertically assembled red-green–blue (RGB) pixels, and quantum dot conversion. For neuroscience studies, these micro-LEDs can be integrated in flexible probes as implantable light sources, which facilitate light delivery into the deep brain tissue for optogenetic stimulations and biological sensing. Additionally, micro-LEDs have the potential to function as wireless biosensors to detect changes in the biological environment, through their luminescence or in combination with other devices. Overall, advanced manufacturing techniques produce micro-LEDs that promise significant applications not only in displays but also in various biomedical fields.

Optogenetics 2.0: challenges and solutions towards a quantitative probing of neural circuits.

To exploit the full potential of optogenetics, we need to titrate and tailor optogenetic methods to emulate naturalistic circuit function. For that, the following prerequisites need to be met: first, we need to target opsin expression not only to genetically defined neurons per se, but to specifically target a functional node. Second, we need to assess the scope of optogenetic modulation, i.e.the fraction of optogenetically modulated neurons. Third, we need to integrate optogenetic control in a closed loop setting. Fourth, we need to further safe and stable gene expression and light delivery to bring optogenetics to the clinics. Here, we review these concepts for the human and rodent brain.

Comparison of Wavelength-Dependent Penetration Depth of 532 nm and 660 nm Lasers in Different Tissue Types.

Introduction: The depth of laser light penetration into tissue is a critical factor in determining the effectiveness of photodynamic therapy (PDT). However, the optimal laser light penetration depth necessary for achieving maximum therapeutic outcomes in PDT remains unclear. This study aimed to assess the effectiveness of laser light penetration depth at two specific wavelengths, 532 nm and 660 mm. Methods: Chicken and beef of different thicknesses (1, 3, 5, 10, and 20 mm±0.2 mm) were used as in vitro tissue models. The samples were subjected to irradiation by a low-level laser diode of 532 and 660 nm in continuous mode for 10 minutes. with power densities of 167 and 142 J/cm2, respectively. Laser light transmission through the tissue was measured using a power meter. Results: For beef samples, the 660 nm wavelength achieved a maximum transmission intensity of 30.7% at 1 cm thickness, while the 532 nm laser had a transmission intensity of 6.5%. Similarly, in chicken breast samples, the maximum transmission occurred at 1 cm thickness with 68.1% for the 660 nm wavelength and 18.2% for the 532 nm laser. Conclusion: Results consistently demonstrated a significant correlation (P<0.05) between tissue thickness and laser light penetration. Thicker tissues exhibited faster declines in light transmission intensity compared to thinner tissues within 10 minutes. These findings highlight the importance of further research to enhance light delivery in thicker tissues and improve the efficacy of PDT in various medical conditions.

A self-powered wireless detachable drug/light injector for metronomic photodynamic therapy in cancer treatment

Cancer is a growing global health concern, and photodynamic therapy (PDT) has emerged as a promising technology with minimal side effects for cancer treatment. Miniaturized PDT devices that offer a flexible and convenient strategy for the low-dose delivery of light or drugs are needed to replace invasive optical fibers. Here, we present a self-powered, wireless, and detachable drug/light injector that conforms to the properties of metronomic PDT for cancer treatment. The device comprises a semi-invasive pedestal with a micro light emitting diode (μ-LED) and a syringe needle, and a detachable actuator that contains a drug reservoir, a thermally-driven pump, and a wireless control circuit. The two parts are magnetically attracted to each other, and the detachable actuator can be conveniently replaced or refilled with drugs. The device can be wirelessly controlled to deliver on-demand dosages of drugs and light into the tumor under the skin. Additionally, we further demonstrate that the device can in principle be partially self-powered using body motion energy upon connection to different piezoelectric nanogenerators. In-vitro and in-vivo experiments on mice have demonstrated the feasibility of the device's therapeutic regimen for implementing metronomic PDT. The average volume of tumors in the treatment group was reduced by 57.4 % compared to the control group. This device has potential applications in future clinical cancer treatment and can expand the scope of self-powered systems for biomedical engineering.

Agar-based optical sensors for electric current measurements

Biodegradable optical waveguides are breakthrough technologies to light delivery and sensing in biomedical and environmental applications. Agar emerges as an edible, soft, low-cost, and renewable alternative to traditional biopolymers, presenting remarkable optical and mechanical characteristics. Previous works introduced agar-made optical fibers for chemical measurements based on their inherent response to humidity and surrounding concentration. Therefore, we propose, for the first time, an all-optical, biodegradable electric current sensor. As flowing charges heat the agar matrix and modulate its refractive index, we connect the optical device to a DC voltage source using pin headers and excite the agar sample with coherent light to project spatiotemporally deviating speckle fields. Experiments proceeded with spheres and no-core fibers comprising 2 wt% agar/water. Once the increasing current stimulates the speckles’ motion, we acquire such images with a camera and evaluate their correlation coefficients, yielding exponential decay-like functions whose time constants provide the input amperage. Furthermore, the light granules follow the polarization of the applied voltage drop, providing visual information about the current direction. The results indicate a maximum resolution of sim 0.4 upmu A for electrical stimuli le 100 upmu A, which fulfills the requirements for bioelectrical signal assessment.

Optogenetic stimulation probes with single-neuron resolution based on organic LEDs monolithically integrated on CMOS

The use of optogenetic stimulation to evoke neuronal activity in targeted neural populations—enabled by opsins with fast kinetics, high sensitivity and cell-type and subcellular specificity—is a powerful tool in neuroscience. However, to interface with the opsins, deep-brain light delivery systems are required that match the scale of the spatial and temporal control offered by the molecular actuators. Here we show that organic light-emitting diodes can be combined with complementary metal–oxide–semiconductor technology to create bright, actively multiplexed emissive elements. We create implantable shanks in which 1,024 individually addressable organic light-emitting diode pixels with a 24.5 µm pitch are integrated with active complementary metal–oxide–semiconductor drive and control circuitry. This integration is enabled by controlled electrode conditioning, monolithic deposition of the organic light-emitting diodes and optimized thin-film encapsulation. The resulting probes can be used to access brain regions as deep as 5 mm and selectively activate individual neurons with millisecond-level precision in mice.

A flexible optoacoustic blood ‘stethoscope’ for noninvasive multiparametric cardiovascular monitoring

Quantitative and multiparametric blood analysis is of great clinical importance in cardiovascular disease diagnosis. Although there are various methods to extract blood information, they often require invasive procedures, lack continuity, involve bulky instruments, or have complicated testing procedures. Flexible sensors can realize on-skin assessment of several vital signals, but generally exhibit limited function to monitor blood characteristics. Here, we report a flexible optoacoustic blood ‘stethoscope’ for noninvasive, multiparametric, and continuous cardiovascular monitoring, without requiring complicated procedures. The optoacoustic blood ‘stethoscope’ features the light delivery elements to illuminate blood and the piezoelectric acoustic elements to capture light-induced acoustic waves. We show that the optoacoustic blood ‘stethoscope’ can adhere to the skin for continuous and non-invasive in-situ monitoring of multiple cardiovascular biomarkers, including hypoxia, intravascular exogenous agent concentration decay, and hemodynamics, which can be further visualized with a tailored 3D algorithm. Demonstrations on both in-vivo animal trials and human subjects highlight the optoacoustic blood ‘stethoscope’‘s potential for cardiovascular disease diagnosis and prediction.

Cancer phototherapy with nano-bacteria biohybrids.

The utilization of light for therapeutic interventions, also known as phototherapy, has been extensively employed in the treatment of a wide range of illnesses, including cancer. Despite the benefits of its non-invasive nature, phototherapy still faces challenges pertaining to the delivery of phototherapeutic agents, phototoxicity, and light delivery. The incorporation of nanomaterials and bacteria in phototherapy has emerged as a promising approach that leverages the unique properties of each component. The resulting nano-bacteria biohybrids exhibit enhanced therapeutic efficacy when compared to either component individually. In this review, we summarize and discuss the various strategies for assembling nano-bacteria biohybrids and their applications in phototherapy. We provide a comprehensive overview of the properties and functionalities of nanomaterials and cells in the biohybrids. Notably, we highlight the roles of bacteria beyond their function as drug vehicles, particularly their capacity to produce bioactive molecules. Despite being in its early stage, the integration of photoelectric nanomaterials and genetically engineered bacteria holds promise as an effective biosystem for antitumor phototherapy. The utilization of nano-bacteria biohybrids in phototherapy is a promising avenue for future investigation, with the potential to enhance treatment outcomes for cancer patients.

Ex Vivo Optical Properties Estimation for Reliable Tissue Characterization

: Lasers are demonstrating high impact in many medical and biological applications. They have different interaction mechanisms within tissues depending on operational parameters, particularly the wavelength. In addition, the optical properties of the examined tissue (i.e., absorption and scattering properties) influence the efficacy of the applied laser. The development of optical biomedical techniques relies on the examination of tissues’ optical properties, which describe the viability of tissue optical evaluation and the effect of light on the tissue. Understanding the optical properties of tissues is necessary for the interpretation and evaluation of diagnostic data, as well as the prediction of light and energy absorption for therapeutic and surgical applications. Moreover, the accuracy of many applications, including tissue removal and coagulation, depends on the tissues' spectroscopic characteristics. In the current paper, a set of ex vivo absorption and scattering coefficients of different types of biological samples (skin, skull, liver and muscle) at 650 nm laser irradiation were retrieved using an integrating phere system paired with the Kubelka–Munk model. The obtained optical parameters were utilized to acquire the local fluence rate within the irradiated tissues based on the Monte Carlo simulation method and the diffusion approximation of the radiative transfer equation. The obtained results reveal that the optical absorption and scattering coefficients control the light propagation and distribution within biological tissues. Such an understanding refers to system design optimization, light delivery accuracy and the minimization of undesirable physiological effects such as phototoxicity or photobleaching.

Miniaturized Stacked Transducer for Intravascular Sonothrombolysis With Internal-Illumination Photoacoustic Imaging Guidance and Clot Characterization.

Thromboembolism in blood vessels can lead to stroke or heart attack and even sudden death unless brought under control. Sonothrombolysis enhanced by ultrasound contrast agents has shown promising outcome on effective treatment of thromboembolism. Intravascular sonothrombolysis was also reported recently with a potential for effective and safe treatment of deep thrombosis. Despite the promising treatment results, the treatment efficiency for clinical application may not be optimized due to the lack of imaging guidance and clot characterization during the thrombolysis procedure. In this paper, a miniaturized transducer was designed to have an 8-layer PZT-5A stacked with an aperture size of 1.4 × 1.4 mm2 and assembled in a customized two-lumen 10-Fr catheter for intravascular sonothrombolysis. The treatment process was monitored with internal-illumination photoacoustic tomography (II-PAT), a hybrid imaging modality that combines the rich contrast of optical absorption and the deep penetration of ultrasound detection. With intravascular light delivery using a thin optical fiber integrated with the intravascular catheter, II-PAT overcomes the penetration depth limited by strong optical attenuation of tissue. In-vitro PAT-guided sonothrombolysis experiments were carried out with synthetic blood clots embedded in tissue phantom. Clot position, shape, stiffness, and oxygenation level can be estimated by II-PAT at clinically relevant depth of ten centimeters. Our findings have demonstrated the feasibility of the proposed PAT-guided intravascular sonothrombolysis with real-time feedback during the treatment process.

Clinical assessment of a low-cost, hand-held, smartphone-attached intraoral imaging probe for 5-aminolevulinic acid photodynamic therapy monitoring and guidance.

India has one of the highest rates of oral squamous cell carcinoma (OSCC) in the world, with an incidence of 15 per 100,000 and more than 70,000 deaths per year. The problem is exacerbated by a lack of medical infrastructure and routine screening, especially in rural areas. New technologies for oral cancer detection and timely treatment at the point of care are urgently needed. Our study aimed to use a hand-held smartphone-coupled intraoral imaging device, previously investigated for autofluorescence (auto-FL) diagnostics adapted here for treatment guidance and monitoring photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence (FL). A total of 12 patients with 14 buccal mucosal lesions having moderately/well-differentiated micro-invasive OSCC lesions ( diameter and depth) were systemically (in oral solution) administered three doses of ALA (total ). Lesion site PpIX and auto-FL were imaged using the multichannel FL and polarized white-light oral cancer imaging probe before/after ALA administration and after light delivery (fractionated, total of 635nm red LED light). The handheld device was conducive for access to lesion site images in the oral cavity. Segmentation of ratiometric images in which PpIX FL is mapped relative to auto-FL enabled improved demarcation of lesion boundaries relative to PpIX alone. A relative FL (-value) threshold of 1.4 was found to segment lesion site PpIX production among the patients with mild to severe dysplasia malignancy. The segmented lesion size is well correlated with ultrasound findings. Lesions for which -value was at the time of treatment were associated with successful outcomes. These results indicate the utility of a low-cost, handheld intraoral imaging probe for image-guided PDT and treatment monitoring while also laying the groundwork for an integrated approach, combining cancer screening and treatment with the same hardware.

Ultra-Short Laser Pulses Propagation Through Mouse Head Tissues: Experimental and Computational Study

We present a prototype and verification of a multichannel laser system applicable to optogenetic research. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">In vivo</i> photostimulation of neural cells expressing photoconvertible phytochromes or opsins requires enough light irradiation delivery to the brain that cannot be supported by continues-wave (CW) light sources. The use of ultra-short pulsed (USP) lasers operating in the second near-infrared region (II-NIR) and allowing nonlinear activation and deactivation of the photoactuators is a promising method that allows to increase the penetration depth and provide spatio-temporal localisation of radiation in tissues. This study aimed to investigate the efficiency of USP light propagation in the skin, skull, and brain of the mouse head, as well as to compare it with the corresponding CW radiation propagation in the 750–830 nm and 1086–1183 nm wavelength ranges. The experimental results and computer modelling demonstrate that about 10–12% of the initial laser radiation can reach the brain tissues. These results prove that under certain conditions, the USP laser radiation can reach a penetration depth with required power that will be sufficient for non-linear activation of opsins/phytochromes in the brain of living animals.

Transdermal tibial nerve optogenetic stimulation targeting C-fibers.

Purpose: To explore whether stimulation of C-fibers in tibial nerves can induce bladder inhibition by optogenetic transdermal illumination. Methods: Ten rats were injected with AAV2/6-hSyn-ChR2(H134R)-EYFP into the tibial nerves. Transurethral cystometry was performed 4 weeks after the virus injection. Illumination (473-nm blue light at 100mW) was performed with the fiber positioned above the right hind paw near the ankle. The light transmission efficiency was examined with a laser power meter. The effects on cystometry were compared before and after illumination with the bladder infused with normal saline and acetic acid, respectively. Result: Upon transdermal delivery of 473-nm light at a peak power of 100mW, the irradiance value of 0.653mW/mm2 at the target region was detected, which is sufficient to activate opsins. The photothermal effect of 473-nm light is unremarkable. Acute inhibitory responses were not observed during stimulation regarding any of the bladder parameters; whereas, after laser illumination for 30min, a statistically significant increase in bladder capacity with the bladder infused with normal saline (from 0.53 ± 0.04mL to 0.72 ± 0.05mL, p < 0.001) and acetic acid (from 0.25 ± 0.02mL to 0.37 ± 0.04mL, p < 0.001) was detected. A similar inhibitory response was observed with pulsed illumination at both 10Hz and 50Hz. However, illumination did not significantly influence base pressure, threshold pressure, or peak pressure. Conclusion: In this preliminary study, it can be inferred that the prolonged bladder inhibition is mediated by the stimulation of C-fibers in the tibial nerves, with no frequency-dependent characteristics. Although the 473-nm blue light has limited penetration efficacy, it is sufficient to modulate bladder functions through transdermal illumination on the superficial peripheral nervous system.